Similarly High Response Rates Found With Four Monoclonal Antibodies in Plaque Psoriasis

By Will Boggs MD

February 18, 2020

NEW YORK (Reuters Health) - Brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa provide the highest response rates in both short-term and long-term therapy of plaque psoriasis, according to a new study.

Numerous biologics and oral treatments have been shown to provide substantial benefits to patients with plaque psoriasis, but head-to-head trials are not available for many combinations, making it challenging for clinicians to determine how the medications compare with one another.

Dr. April W. Armstrong of the University of Southern California, in Los Angeles, and colleagues evaluated the comparative efficacy of systemic treatments for psoriasis, including newly developed biologics, in a network meta-analysis (NMA) of 60 studies of anti-TNF agents, anti-IL-23 agents, anti-IL-17 agents, apremilast, and ustekinumab.

The estimated Psoriasis Area and Severity Index (PASI) 75, 90 and 100 response rates at the end of the primary response period 10 to 16 weeks from baseline were highest for brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa, with no significant differences among these treatments.

For PASI 90, for example, the rates were around 70%, Dr. Armstrong and colleagues report in JAMA Dermatology.

Similarly, the highest PASI 75, 90 and 100 response rates during long-term maintenance (44 to 60 weeks from baseline) occurred following treatment with one of these four drugs or secukinumab.

"In the absence of head-to-head randomized clinical trials of treatments for moderate to severe plaque psoriasis, this study provides what we believe to be a comprehensive assessment of the comparative short-term and long-term efficacy among several novel treatments," the authors conclude.

"Meta-analysis efficacy comparisons are helpful in grouping the short-term efficacy of available drugs and do so by broadly categorizing them as super high, high, modest, and low performing," write Dr. Bruce Strober of Yale University School of Medicine, in New Haven, Connecticut, and Dr. Kenneth B. Gordon of the Medical College of Wisconsin, in Milwaukee, in a linked editorial.

"However, what is left to the reader is determining the clinical relevance of small distinctions between medications that result from these evaluations," they add.

"The raw rankings of efficacy as determined by the Armstrong et al NMA and other recently published NMAs offer a valuable starting point from which to initiate discussions with patients and improve shared decision making related to choosing the most appropriate psoriasis treatment," they conclude.

In another study in JAMA Dermatology, researchers compared six-month improvements in PASI among 234 children with plaque psoriasis treated with methotrexate or biologics.

Methotrexate was used three times as often as biologics in North America and twice as often in Europe, Dr. Inge M. G. J. Bronckers of Radboud University, in Nijmegen, the Netherlands, and colleagues report.

At six months, significantly more patients treated with biologics (20/28, 71.4%) than with methotrexate (12/30, 40.0%) achieved PASI 75. Also, more patients treated with biologics (18/37, 48.6%) than with methotrexate (41/115, 35.6%) achieved clear skin or minimal disease, but this difference fell short of statistical significance.

At the data cutoff, 35.3% (66/187) of methotrexate patients had discontinued treatment (19.3% for ineffectiveness, 11.8% for adverse events, and 3.7% for nonadherence), compared with 22.5% (16/71) of biologics patients (15.5% for ineffectiveness and 5.6% for adverse events).

Drug survival owing to ineffectiveness was comparable between the treatment groups, but discontinuations due to adverse events were nearly five times more frequent with methotrexate.

"Methotrexate and biologics appear to be associated with improvement in pediatric psoriasis, although biologics seem to be associated with greater reduction in psoriasis severity scores and higher drug survival rates than methotrexate in the real-world setting," the authors conclude. "Additional studies directly comparing these medications should be performed for confirmation."

None of the corresponding authors responded to a request for comments.

AbbVie funded the meta-analysis and employed three of the authors. The company also had various relationships with the authors of the editorial. Likewise, many of the authors of the pediatric study had ties to companies that manufacture treatments for plaque psoriasis.

SOURCE: https://bit.ly/2UUBcOd, https://bit.ly/2SJ1YpQ and https://bit.ly/37lRsdC JAMA Dermatology, online February 5, 2020.

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